Arabidopsis ATG8-INTERACTING PROTEIN1 Is Involved in Autophagy-Dependent Vesicular Trafficking of Plastid Proteins to the Vacuole

Selective autophagy has been extensively studied in various organisms, but knowledge regarding its functions in plants, particularly in organelle turnover, is limited. We have recently discovered ATG8-INTERACTING PROTEIN1 (ATI1) from Arabidopsis thaliana and showed that following carbon starvation it is localized on endoplasmic reticulum (ER)-associated bodies that are subsequently transported to the vacuole. Here, we show that following carbon starvation ATI1 is also located on bodies associating with plastids, which are distinct from the ER ATI bodies and are detected mainly in senescing cells that exhibit plastid degradation. Additionally, these plastid-localized bodies contain a stroma protein marker as cargo and were observed budding and detaching from plastids. ATI1 interacts with plastid-localized proteins and was further shown to be required for the turnover of one of them, as a representative. ATI1 on the plastid bodies also interacts with ATG8f, which apparently leads to the targeting of the plastid bodies to the vacuole by a process that requires functional autophagy. Finally, we show that ATI1 is involved in Arabidopsis salt stress tolerance. Taken together, our results implicate ATI1 in autophagic plastid-to-vacuole trafficking through its ability to interact with both plastid proteins and ATG8 of the core autophagy machinery.     

Unraveling seasonality in population averages: an examination of seasonal variation in glucose levels in diabetes patients using a large population-based data set

It has been shown that the population average blood glucose level of diabetes patients shows seasonal variation, with higher levels in the winter than summer. However, seasonality in the population averages could be due to a tendency in the individual to seasonal variation, or alternatively due to occasional high winter readings (spiking), with different individuals showing this increase in different winters. A method was developed to rule out spiking as the dominant pattern underlying the seasonal variation in the population averages. Three years of data from three community-serving laboratories in Israel were retrieved. Diabetes patients (N?=?3243) with a blood glucose result every winter and summer over the study period were selected. For each individual, the following were calculated: seasonal average glucose for all winters and summers over the period of study (2006-2009), winter-summer difference for each adjacent winter-summer pair, and average of these five differences, an index of the degree of spikiness in the pattern of the six seasonal levels, and number of times out of five that each winter-summer difference was positive. Seasonal population averages were examined. The distribution of the individual's differences between adjacent seasons (winter minus summer) was examined and compared between subgroups. Seasonal population averages were reexamined in groups divided according to the index of the degree of spikiness in the individual's glucose pattern over the series of seasons. Seasonal population averages showed higher winter than summer levels. The overall median winter-summer difference on the individual level was 8?mg/dL (0.4?mmol/L). In 16.9% (95% confidence interval [CI]: 15.6-18.2%) of the population, all five winter-summer differences were positive versus 3.6% (95% CI: 3.0-4.2%) where all five winter-summer differences were negative. Seasonal variation in the population averages was not attenuated in the group having the lowest spikiness index; comparison of the distributions of the winter-summer differences in the high-, medium-, and low-spikiness groups showed no significant difference (p?=?.213). Therefore, seasonality in the population average blood glucose in diabetes patients is not just the result of occasional high measurements in different individuals in different winters, but presumably reflects a general periodic tendency in individuals for winter glucose levels to be higher than summer levels.     

Proximate and Elemental Composition of <Emphasis Type="Italic">Chamelea gallina</Emphasis> from the Southern Coast of the Marmara Sea (Turkey)

The venerid clam Chamelea gallina is a popular and economic foodstuff around the Mediterranean countries especially in Italy, Spain, and France. The aim of this study is to evaluate the nutritional quality of striped venus of Southern Marmara. Samples were harvested seasonally at five stations and analyzed to determine meat yield, proximate, and elemental composition. According to the results, meat yield ranged from 20.24% to 29.94%. Means of water, protein, lipid, and ash content were 67%, 10.12%, 2.57%, and 1.66%, respectively. The mean concentrations (mg/kg wet weight) of elements in tissues are as follows: B: 2.37–4.24; Cr: 0–0.76; Co: 0–0.43; Cu: 0.71–5.30; Mn: 0.30–5.94; Zn: 13.08–77.76; Ni: 0–1.22; Fe: 2.46–114.22; Al: 1.23–75.49; Pb: 0.18–3.24; Ba: 0.66–15.97; Cd: 0.04–0.69. Among the reported metal levels, only Pb and Zn in two stations exceeded the maximum critical concentrations enforced by Turkish legislation and European Commission. Therefore, we report that striped venus from Southern Marmara Sea, in general, are safe for human consumption; nonetheless, Pb and Zn levels should be closely monitored in the future.     

Potent and selective adenosine A2A receptor antagonists: 1,2,4-Triazolo[1,5-c]pyrimidines

Antagonism of the adenosine A_2a receptor offers great promise in the treatment of Parkinson’s disease. In the course of exploring pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine A_2A antagonists, which led to clinical candidate SCH 420814, we prepared 1,2,4-triazolo[1,5-c]pyrimidines with potent and selective (vs A₁) A_2a antagonist activity, including oral activity in the rat haloperidol-induced catalepsy model. Structure–activity relationships and plasma levels are described for this series.     

ATI1, a newly identified atg8-interacting protein,binds two different Atg8 homologs

Autophagy is a mechanism used for the transport of macromolecules to the vacuole for degradation. It can be either non-selective or selective, resulting from the specific binding of target proteins to Atg8, an essential autophagy-related protein. Nine Atg8 homologs exist in the model plant Arabidopsis thaliana, suggesting possible different roles for different homologs. In a previous report published in the Plant Cell, our group identified two plant-specific proteins, termed ATI1 and ATI2, which bind Atg8f, as a representative of the nine Atg8 homologs. The proteins were shown to associate with novel starvation-induced bodies that move on the ER network and reach the lytic vacuole. Altered expression level of the proteins was also shown to affect the ability of seeds to germinate in the presence of the germination inhibiting hormone ABA. In the present addendum article, we demonstrate that, in addition to Atg8f, ATI1 binds Atg8h, an Atg8 homolog from a different sub-family, indicating that ATI1 is not a specific target of Atg8f.     

Chromenones as potent bradykinin B1 antagonists

A series of fused 6,6-bicyclic chromenones was investigated for activity against the bradykinin B1 receptor. SAR studies based on a pharmacophore model revealed compounds with high affinity for both human and rabbit B1. These compounds demonstrated favorable pharmacokinetic properties and 5-chlorochromenone 15 was efficacious in a carrageenan-induced mechanical hyperalgesia model for chronic pain.     

The earliest steps in hepatitis B virus infection

The early steps in hepatitis B virus (HBV) infection, a human hepadnavirus, initiates from cell attachment followed by entry and delivery of the genetic information to the nucleus. Despite the fact that these steps determine the virus-related pathogenesis, their molecular basis is poorly understood. Cumulative data suggest that this process can be divided to cell attachment, endocytosis, membrane fusion and post-fusion consecutive steps. These steps are likely to be regulated by the viral envelope proteins and by the cellular membrane, receptors and extracellular matrix. In the absence of animal model for HBV, the duck hepadnavirus DHBV turned out to be a fruitful animal model. Therefore data concerning the early, post-attachment steps in hepadnaviral entry are largely based on studies performed with DHBV in primary duck liver hepatocytes. These studies are now starting to illuminate the mechanisms of hepadnavirus route of cell entry and to provide some new insights on the molecular basis of the strict species specificity of hepadnavirus infection.     

Recombinant viral capsids as an efficient vehicle of oligonucleotide delivery into cells

Delivery of oligonucleotides (ON) into cells is a technical challenge. In this study, we utilized the capsid of the hepatitis B virus (HBV) to meet this goal. A single and short open reading frame of the virus programs efficient capsid production in bacteria. We show that these capsids can encapsulate ON in vitro and then mediate their delivery into cells with extreme efficiency. This process is cell type non-specific, rendering the recombinant HBV capsid a potentially valuable vehicle for ON delivery into a wide range of cultured cells.     

The discovery and synthesis of novel adenosine receptor (A(2A)) antagonists

In high throughput screening of our file compounds, a novel structure 1 was identified as a potent A(2A) receptor antagonist with no selectivity over the A1 adenosine receptor. The structure-activity relationship investigation using 1 as a template lead to identification of a novel class of compounds as potent and selective antagonists of A(2A) adenosine receptor. Compound 26 was identified to be the most potent A(2A) receptor antagonist (Ki = 0.8 nM) with 100-fold selectivity over the A1 adenosine receptor.